The cardiac form of troponin-T (cTnT), a protein that is known to be present in the I-bands of cardiac myocytes, is known to be released into the blood circulation as a consequence of various forms of damage to cardiac myocytes. We have previously shown that release of cTnT into the blood occurs not only in conditions associated with myocardial necrosis, but also in the degenerative type of chronic dilated cardiomyopathy that results from the administration of doxorubicin (a widely used antineoplastic agent of the anthracycline family). We have further shown that the release of cTnT in a model system of doxorubicin-induced cardiomyopathy in spontaneously hypertensive rats (SHR) is proportional to the total cumulative dose of doxorubicin, and that this release is associated with the loss of cTnT from cardiac myocytes, as demonstrated by decreased immunofluorescent staining for cTnT in sections of cardiac tissue. During the past year, additional studies of this problem have led to the following conclusions:1. The doxorubicin-induced loss of cTnT is attenuated considerably by pretreatment of the SHR with dexrazoxane, an agent known to ameliorate the cardiotoxicity of doxorubicin. 2. We have extended these observations to the cardiotoxicity induced in SHR by mitoxantrone, an antineoplastic agent of the anthracenedione family. This compound shares many of the pharmacological properties of doxorubicin, including induction of the release of cTnT from damaged cardiac myocytes.3. The cardiac toxicity of mitoxantrone is also ameliorated by pretreatment with dexrazoxane, and this pretreatment also decreases considerably the mitoxantrone-induced release of cTnT from the myocytes. 4. Evidence obtained in this study suggests that the improvement of mitoxantrone-induced cardiotoxicity is related to the ability of dexrazoxane to remove iron from an iron-mitoxantrone complex that induces the formation of reactive oxygen species that damage the cardiac myocytes.